Tested By

Overview

Carnitine uptake deficieny (CUD) results in urinary carnitine wasting and systemic and intracellular carnitine deficiency.
The latter results in an intramitochondrial defect in the beta-oxidation of fatty acids that impairs energy production and
causes accumulation of free fatty acids. The increased reliance on fat metabolism for energy production during prolonged fasting
and/or periods of increased energy demands (fever, stress, lack of sleep) may cause metabolic crises in patients with carnitine
deficiency. Mutations in the SLC22A5 gene cause CUD. This gene is responsible for making a protein called OCTN2 that transports
carnitine into cells.

Incidence

Approximately 1 in 40,000 [Koizumi: 1999], with about 1% of the normal US population being heterozygous (carriers) for this condition [Amat: 2008]

Inheritance

Autosomal recessive

Prenatal Testing

DNA testing possible by amniocentesis or chorionic villus sampling (CVS) if both disease causing mutations of an affected
family member have been identified. Gunctional assay (carnitine transport) possible by amniocentesis or CVS.

Other Testing

Genetic testing is possible for at-risk family members if both disease causing mutations of an affected family member have
been identified.

Clinical Characteristics

With treatment prior to metabolic crises, outcomes should be normal. Treatment may reverse pre-existing cardiomyopathy and muscle weakness,
but not developmental delay. Without treatment, symptoms may begin between birth and three years of age or, in the myopathic form, symptoms usually begin before seven years
and may not include metabolic crisis episodes or hypoglycemia. Some children remain asymptomatic for life. Patients are at
risk of sudden death from arrhythmia at any age.

Inital signs and symptoms may include:

poor appetite

vomiting

irritability

lethargy

hypoketotic hypoglycemia

sudden death

lab findings:

anemia

metabolic acidosis

hypoglycemia

Subsequent finding include:

muscle weakness

cardiomyopathy

cardiac arrhythmia

hepatomegaly

seizures and

brain injury from hypoglycemia

Treatment consists of carnitine supplementation. Mothers with primary carnitine deficiency can be identified by newborn screening
of their unaffected infant.[Schimmenti: 2007]

Genetics in Primary Care Institute (AAP)The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. It includes
health supervision guidelines and other useful resources; represents a collaboration among the Health Resources & Services
Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

Genetics in Primary Care Institute (AAP)The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. It includes
health supervision guidelines and other useful resources; represents a collaboration among the Health Resources & Services
Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

Helpful Articles

Authors

Page Bibliography

Amat di San Filippo C, Taylor MR, Mestroni L, Botto LD, Longo N.Cardiomyopathy and carnitine deficiency.Mol Genet Metab..
2008;94(2):162-166.
Carnitine is essential for the transfer of long-chain fatty acids across the mitochondrial membrane for subsequent beta-oxidation.
Study results indicate heterozygosity for primary carnitine deficiency is not more frequent in patients with unselected types
of cardiomyopathy and is unlikely to be an important cause of cardiomyopathy in humans.